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Developing genome editing therapies for rare and ultra-rare metabolic diseases Sarah A Grandinette
- Format:
- Book
- Thesis/Dissertation
- Author/Creator:
- Grandinette, Sarah A., author.
- Language:
- English
- Subjects (All):
- Cellular biology.
- Genetics.
- Biochemistry.
- Immunology.
- Virology.
- 0379.
- 0369.
- 0720.
- 0982.
- 0487.
- Local Subjects:
- Cellular biology.
- Genetics.
- Biochemistry.
- Immunology.
- Virology.
- 0379.
- 0369.
- 0720.
- 0982.
- 0487.
- Genre:
- Academic theses
- Physical Description:
- 1 online resource (122 pages)
- Contained In:
- Dissertations Abstracts International 87-12B
- Place of Publication:
- Ann Arbor : ProQuest Dissertations and Theses, 2026
- Language Note:
- English
- Summary:
- Genome editing tools can directly correct pathogenic variants known to cause genetic diseases. Vectors including lipid nanoparticles (LNPs) or recombinant adeno-associated viruses (AAV) can efficiently deliver these editing strategies to the liver in vivo. Inborn errors of metabolism collectively affect 1 in 2000 individuals and are often caused by variants in genes highly expressed in the liver. A deficiency in pathways that involve the breakdown of carbohydrates or proteins can lead to accumulation of toxic metabolites that results in cognitive impairment which affects approximately 80% of patients with inborn errors of metabolism. In vivo genome editing has the potential to therapeutically benefit many patients with metabolic disorders and can be rapidly customized to individual genetic variants. This thesis explores liver-targeted genome editing for the treatment of a prevalent variant that causes classic galactosemia, a rare deficiency of galactose metabolism. This work also highlights the potential for personalized genome editing by developing a therapy for a single patient diagnosed with severe neonatal-onset carbamoyl-phosphate synthetase 1 (CPS1) deficiency within 7 months of birth. This collaborative effort resulted in the treatment of an N-of-1 patient, now widely known as Baby KJ, who demonstrated that multiple doses of an LNP editing therapy were safe in an infant and provided clinical benefit. This story has already inspired a new regulatory pathway for genome editing therapies for rare diseases. Through a similar innovative framework utilizing rapid screening, safety assessments, and a platform approach, bespoke genome editing treatments could quickly become the standard of care for patients with devastating rare metabolic disorders
- Notes:
- Source: Dissertations Abstracts International, Volume: 87-12, Section: B.
- Advisors: Musunuru, Kiran Committee members: Ahrens-Nicklas, Rebecca; George, Lindsey; Kaestner, Klaus; Peranteau, William
- Ph.D. University of Pennsylvania 2026
- Vendor supplied data
- Local Notes:
- School code: 0175
- ISBN:
- 9798247980421
- Access Restriction:
- Restricted for use by site license
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